Laminin chains in rat and human peripheral nerve: Distribution and regulation during development and after axonal injury

During nerve growth, axons are dependent upon contact with matrix components, such as laminins, for elongation, guidance, and trophic support. Semiquantitative in situ hybridization histochemistry and immunohistochemistry (IHC) were used to identify laminin chains in normal peripheral nerves, during postnatal development, after sciatic nerve transection (SNT), and after sciatic nerve crush (SNC). Laminin alpha2, alpha4, beta1, beta2, and gamma1 chain mRNAs were all expressed at high levels in newborn rat sciatic nerves with declining levels during later developmental stages. At the adult stage, no laminin chain mRNA was detectable. Of interest, the mRNA levels for alpha4 chain declined faster than those for alpha2. After SNT, laminin alpha2, alpha4, beta1, and gamma1 mRNA levels were up-regulated at the site of the injury, with the most profound reaction in the proximal nerve stump. Laminin alpha2 and alpha4 chains differed in that the mRNA levels of alpha4 were up-regulated earlier and declined quicker, whereas alpha2 had a later onset, with high levels remaining even after 6 weeks. After SNC, there was an initial up-regulation of the same laminin chain mRNAs as after SNT in the nerve, however, less intense, and at 6 weeks after SNC, all laminin mRNA levels studied had returned to normal. IHC of adult human normal and transected peripheral nerves stained positive for laminin alpha2, alpha4, beta1, and gamma1 chains in close relation to neurofilament labeled axons. Laminin alpha3, alpha4, alpha5, beta1, beta2, and gamma1 chains were found in blood vessel-like structures and alpha3, alpha4, alpha5, beta2, and gamma1 in the perineurium. These results and a previously published description of integrin regulation in spinal motoneurons suggest that both laminin-2 (alpha2beta1gamma1) and laminin-8 (alpha4beta1gamma1) are important for the postnatal nerve development and axonal regeneration after injury and that laminin-8 may have important functions especially early postnatally and early after adult nerve lesion.